Regulation of isolation membrane remodelling during autophagosome biogenesis by sorting nexins

自噬描述了细胞自我吞噬的有趣而重要的过程。它存在于从酵母到人类的各种生物中，进一步证明了它对动物、植物和真菌王国的细胞的重要性。细胞利用自噬产生能量和物质，以便在不利条件下生存。他们也用这个过程来处理受损和潜在有毒的细胞成分。这对于长寿命的细胞尤其重要，比如我们大脑中的神经元，它们必须应对多年来作为细胞功能正常结果而发生的累积损伤。我们现在对细胞中自噬是如何触发的以及负责自噬体形成的分子（自噬体是一种膜结合载体，是自噬途径的功能单位）有了很多了解，但我们仍然不了解这些结构是如何在细胞内组装的。有一个大家族的蛋白质被称为分类连接蛋白（SNXs），在重塑我们细胞内现有的膜中起着重要的作用。我们有初步证据表明其中一些蛋白质在自噬中起作用，现在希望详细了解这些蛋白质是如何起作用的。我们将使用最先进的显微镜和生化分析来描述SNXs如何调节处于饥饿状态或试图去除有毒内含物的细胞中的自噬。这些研究将极大地促进我们对自噬过程中膜动力学的理解。

Autophagy describes the intriguing and essential process of cellular self-eating. It is found in organisms ranging from yeast to man, further demonstrating its importance for cells across the animal, plant and fungal Kingdoms. Cells use autophagy to generate energy and materials in order to survive when conditions become unfavourable. They also use this process to dispose of damaged and potentially toxic cellular components. This is particularly important in long-lived cells such as the neurons in our brains which have to cope over many years with the cumulative damage that occurs as a normal consequence of cellular function. We now know much about how autophagy is triggered in cells and the molecules responsible for the formation of autophagosomes - the membrane-bound vehicles that are the functional units of the autophagy pathway - but we still do not understand how these structures are assembled within cells. There exists a large family of proteins called sorting nexins (SNXs) that play important roles in remodelling existing membranes within our cells. We have preliminary evidence for a role for some of these in autophagy, and now wish to understand in detail how these proteins act. We will use state-of-the-art microscopy and biochemical assays to describe how SNXs regulate autophagy in cells that are undergoing starvation or are attempting to remove toxic inclusions. These studies will significantly advance our understanding of membrane dynamics during autophagy.